The present invention relates to a foamable antifungal composition for the treatment of various skin conditions.
Antifungal agents are well known, and include macrolide antibiotics such as griseofulvin, and imidazoles such as clotrimazole and ketoconazole.
Ketoconazole was originally described by Heeres et al in U.S. Pat. No. 4,335,125, in which its principal utility was an antifungal compound useful in the treatment of a variety of conditions including sebborheic dermatitis, dandruff, “jock itch” and tinea.
Antifungal compositions are traditionally applied as lotions or creams. There are however disadvantages to these forms. In particular, the formulations are frequently very viscous requiring substantial rubbing to achieve penetration into the effected area, an act in itself which causes discomfort and sometimes irritation. If the viscous formulations are not vigorously applied, the active antifungal agent does not necessarily reach the site requiring treatment being the epidermis of the skin. Non-viscous creams and lotions are wont to flow off the effected site before penetration is achieved. One final disadvantage is that cream and lotion bases in themselves can add to site irritation depending on their content.
Ketoconazole was disclosed in U.S. Pat. No. 4,569,935 to be useful in the topical treatment of psoriasis and seborrheic dermatitis. Pursuant to this utility, ketoconazole has been marketed in a 2% shampoo formulation for the treatment of scaling due to dandruff, sold under the brand name “Nizoral®”. This shampoo is applied by the user and then removed shortly, for example 3-5 minutes, after its application by rinsing with water. The active agent is thus only in contact with the area to be treated for a very limited time.
Another patent describing ketoconazole based shampoos is U.S. Pat. No. 5,456,851 in the name of JOHNSON & JOHNSON CONSUMER PRODUCTS, INC which aims to provide good cosmetic properties to the shampoo including lather, and to retard degradation of the ketoconazole. This composition is a foaming formulation.
The disadvantage of such shampoo formulations is that during normal usage, the formulation does not remain on the scalp for a period of time sufficient to allow the antifungal agent to achieve its maximal therapeutic effect since they are designed to be applied, for example in the shower or bath, and shortly after rinsed off with water. Typically, the application instructions for such shampoos suggest that the formulation be removed after 3-5 minutes.
In order to achieve maximal therapeutic effect, one alternative such as is described in AU 80257/87, is to provide a high quantity of residual solids which remain after application to treat the offending skin condition. There is disclosed in AU 80257/87 a foam composition for the delivery of minoxidil. The formulations disclosed in this document all contain a high percentage of non-volatile residues, including propylene glycol. While it is not disclosed why these formulations contain such a large amount of propylene glycol, it is postulated that the propylene glycol is probably required either to enhance the penetration and/or to improve the solubility of the minoxidil. The disadvantage of a composition with a high residual content is that the non-volatile residues are retained at the site of application and therefore feel unpleasant and unattractive to the user.
Alternatives to ketoconazole and minoxidil are described in AU-A-35717/93 in the name of SMITH KLINE BEECHAM PLC which discloses compositions including a novel androstene steroid for use in the treatment of acne and sebborrhea, and AU-A-48851/96 in the name of MEDEVA PLC which describes the use of betamethasone in a quick breaking foam including a buffering agent for use in the treatment of skin diseases and particularly scalp psoriasis.
It is an aim of this invention to provide an antifungal composition which is effective in its treatment of fungal skin conditions but which is also pleasant to use.